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Chapter 24: Antiseizure Drugs

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A 9-year-old child is having learning difficulties at school. He has brief lapses of awareness with eyelid fluttering that occur every 5–10 min. Electroencephalogram (EEG) studies reveal brief 3-Hz spike and wave discharges appearing synchronously in all leads. Which drug would be effective in this child without the disadvantages of excessive sedation or tolerance development?

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(A) Clonazepam

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(B) Diazepam

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(C) Ethosuximide

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(D) Gabapentin

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(E) Phenobarbital

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This child suffers from absence seizures, and 2 of the drugs listed are effective in this seizure disorder. Clonazepam is effective but exerts troublesome CNS-depressant effects, and tolerance develops with chronic use. Ethosuximide is not excessively sedating, and tolerance does not develop to its antiseizure activity. Valproic acid (not listed) is also used in absence seizures. The answer is C.

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Which statement concerning the proposed mechanisms of action of anticonvulsant drugs is inaccurate?

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(A) Benzodiazepines facilitate GABA-mediated inhibitory actions

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(B) Ethosuximide selectively blocks potassium ion (K+) channels in thalamic neurons

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(C) Phenobarbital has multiple actions, including enhancement of the effects of GABA, antagonism of glutamate receptors, and blockade of sodium ion (Na+) channels

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(D) Phenytoin prolongs the inactivated state of the Na+ channel

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(E) Zonisamide blocks voltage-gated Na+ channels

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The mechanism of action of phenylsuccinimides such as ethosuximide involves blockade of T-type Ca2+ channels in thalamic neurons. Ethosuximide does not block K+ channels, which in any case would be likely to result in an increase (rather than a decrease) in neuronal excitability. The answer is B.

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Which drug used in management of seizure disorders is most likely to elevate the plasma concentration of other drugs administered concomitantly?

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(A) Carbamazepine

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(B) Clonazepam

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(C) Phenobarbital

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(D) Phenytoin

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(E) Valproic acid

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With chronic use, carbamazepine, phenobarbital, and phenytoin can induce the synthesis of hepatic drug-metabolizing enzymes. This action may lead to a decrease in the plasma concentration of other drugs used concomitantly. Valproic acid, an inhibitor of drug metabolism, can increase the plasma levels of many drugs, including those used in seizure disorders such as carbamazepine, lamotrigine, phenobarbital, and phenytoin. Benzodiazepines (including clonazepam and diazepam) as well as gabapentin ...

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